B6.Cg-Commd10^{Tg(Vav1-icre)A2Kio}/J

Stock number: 008610
Product name: Vav-iCre
Research areas: Cancer Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Vav-iCre transgenic mice have the mouse HS21/45 control regions directing expression of an optimized variant of Cre recombinase (iCre) to hematopoietic cells (and their progenitors), and may be useful for generating conditional mutations in hematopoietic cells.

In Goodwin et al. 2019 Genome Res. 29:494, it was discovered that the transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18 - creating a Commd10 null allele.

Detailed description

Vav-iCre transgenic mice express an improved Cre recombinase (iCre) under the control of the mouse vav 1 oncogene (Vav1) promoter. The transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18. The insertion results in a functional knock-out of Commd10 in homozygous mice.

Mice hemizygous for this Vav-iCre transgene are viable and fertile, with the mouse HS21/45-vav control regions directing expression of an optimized variant of Cre recombinase (iCre) to hematopoietic cells (and their progenitors). Using crosses to a reporter strain, variegated germ line (testis and ovaries), and heart and gut expression is also reported. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequence(s) in the offspring. These Vav-iCre transgenic mice may be useful for generating conditional mutations in hematopoietic cells.

Joseph et al. 2013 Cell Stem Cell 13:520 reports that Vav-iCre mice express iCre in hematopoietic cells and endothelial cells, as well as in the testes. For Cre-lox experiments and to avoid/minimize germline deletion of the floxed allele, researchers may consider breeding Vav-iCre females with floxed males. However, female germline expression may also be observed (see below).

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry (Commd10^{Tg(Vav1-icre)A2Kio}). This same information would also be found searching the MGI Recombinase Activity database.

This Vav-iCre strain (Stock No. 008610) allows reliable deletion of specific genes throughout the entire hematopoietic compartment, whereas the hCD2-iCre strain (Stock No. 008520) allows targeting to be focused to T cells and B cells.

Development

The Vav-iCre transgene was designed with the mouse vav 1 oncogene (Vav1) promoter region (containing the 2 proximal upstream DNase-I hypersensitive (HS) sites (HS21)), an optimized variant of Cre recombinase (iCre; improved with mammalian codon usage, removed putative cryptic splce sites, altered stop codon, and reduced CpG content to limit the chances of epigenetic silencing in mammals) and an SV40 polyA signal replacing Vav1 exon 1, and Vav1 intron 1 (containing both proximal HS sites (HS45)). The transgene was microinjected into the pronuclei of fertilized oocytes from (CBA/Ca x C57BL/10)F1 mice. Founder mice (founder line ".A2") were established and used to generate mutant mice. The resulting Vav-iCre transgenic mice were subsequently bred to wildtype C57BL/6 mice for more than 16 generations prior to arrival at The Jackson Laboratory Repository. Upon arrival, the Vav-iCre transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony. As of 2015, SNP testing mice from several pedigree lines showed all 5 markers determining C57BL/6 substrain to be C57BL/6J allele-type.
In 2018, it was discovered that the transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18 - creating a Commd10 null allele.

Allele

Symbol: Commd10^{Tg(Vav1-icre)A2Kio}
Name: transgene insertion A2, Dimitris Kioussis
MGI accession ID: MGI:2449949
Generation method: Transgenic
Attributes: Recombinase-expressing; Null/Knockout
Marker symbol: Commd10
Marker name: COMM domain containing 10
Chromosome: 18
Strain of origin: (CBA/Ca x C57BL/10)F2
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase is expressed in lymph nodes, thymus, spleen, Peyer's patches, intestinal cryptopatches, ovaries and testes.
Molecular note: This transgene expresses Cre recombinase under the control of a vav promoter. This promoter was shown to be active in lymph nodes, thymus, spleen, Peyer's patches, intestinal cryptopatches, ovaries and testes. Line A2 inserted into the gene at 47022629-47022630 (Build GRCm38/mm10). The insetion results in a functional knock-out in homozygous mice.